Modern era systemic therapies: Expanding concepts of cure in early and locally advanced non-small cell lung cancer.

Cure of cancer is a sensitive and multidimensional concept that is challenging to define, difficult to assert at the individual patient level, and often surrounded by controversy. The notion of cure in non-small cell lung cancer (NSCLC) has changed and continues to evolve with improvements in diagnosis and treatment. Targeted and immune therapies have recently entered the treatment landscape of stage I-III NSCLC. While some initial pivotal trials of such agents failed to improve survival, recently approved epidermal growth factor receptor (EGFR) inhibitors (in EGFR-mutated NSCLC) and immune checkpoint inhibitors have shown delays in disease recurrence or progression and unprecedented survival gains compared to previous standards of care. Additional data is now emerging supporting the benefit of treatment strategies based on alternation-matched targeting (anaplastic lymphoma kinase [ALK] inhibition in ALK-altered disease) and immune checkpoint inhibition in stage I-III NSCLC. Similar to previous developments in the treatment of early and locally advanced NSCLC, it is expected that statistically significant and clinically meaningful trial-level benefits will translate into real-world benefits, including improvements in cure measures. Parallel advances in molecular testing (e.g., circulating tumor DNA analyses) are also allowing for a deeper and more comprehensive characterization of disease status and treatment response. Given the impact that curative-intent treatments have on survival, it is critical that various stakeholders, including clinicians and patients, are aware of new opportunities to pursue cure in stage I-III NSCLC.

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).

Recommendations to Improve Management of Incidental Pulmonary Nodules in Canada: Expert Panel Consensus.

Introduction: Incidental pulmonary nodules (IPN) are common radiologic findings, yet management of IPNs is inconsistent across Canada. This study aims to improve IPN management based on multidisciplinary expert consensus and provides recommendations to overcome patient and system-level barriers. Methods: A modified Delphi consensus technique was conducted. Multidisciplinary experts with extensive experience in lung nodule management in Canada were recruited to participate in the panel. A survey was administered in 3 rounds, using a 5-point Likert scale to determine the level of agreement (1 = extremely agree, 5 = extremely disagree). Results: Eleven experts agreed to participate in the panel; 10 completed all 3 rounds. Consensus was achieved for 183/217 (84.3%) statements. Panellists agreed that radiology reports should include a standardized summary of findings and follow-up recommendations for all nodule sizes (ie, <6, 6-8, and >8 mm). There was strong consensus regarding the importance of an automated system for patient follow-up and that leadership support for organizational change at the administrative level is of utmost importance in improving IPN management. There was no consensus on the need for standardized national referral pathways, development of new guidelines, or establishing a uniform picture archiving and communication system. Conclusion: Canadian IPN experts agree that improved IPN management should include standardized radiology reporting of IPNs, standardized and automated follow-up of patients with IPNs, guideline adherence and implementation, and leadership support for organizational change. Future research should focus on the implementation and long-term effectiveness of these recommendations in clinical practice.

From mouthpiece of an emerging specialty to voice for high-quality research: the first 100 years of the British Journal of Anaesthesia.

The British Journal of Anaesthesia (BJA) celebrates its centenary in 2023, and with it 100 yr of continuous anaesthesia research publication. As an editorially and financially independent journal, the BJA faced a rapidly changing anaesthesia profession, health system, and publishing world without the security of institutional support. In its early days, the Journal was vocal about the challenging conditions faced by anaesthetists before the National Health System was established, and was essential in advocating for the specialty. Although the years after World War II brought improving fortunes for the specialty, the BJA found itself struggling to publish. As the Journal's fortunes began to improve, a new research and healthcare context emerged, radically changing the face of anaesthesia research and practice, to which the Journal needed to adapt. In spite of a range of challenges throughout the years, the BJA has developed into an international, future-focused, well-respected publication. This could not have been achieved without continual transformation, and the willingness to take risks and meet the changing times head on.

Accuracy and Prognostic Significance of Oncologists' Estimates and Scenarios for Survival Time in Advanced Gastric Cancer.

BACKGROUND: Worst-case, typical, and best-case scenarios for survival, based on simple multiples of an individual's expected survival time (EST), estimated by their oncologist, are a useful way of formulating and explaining prognosis. We aimed to determine the accuracy and prognostic significance of oncologists' estimates of EST, and the accuracy of the resulting scenarios for survival time, in advanced gastric cancer. MATERIALS AND METHODS: Sixty-six oncologists estimated the EST at baseline for each of the 152 participants they enrolled in the INTEGRATE trial. We hypothesized that oncologists' estimates of EST would be unbiased (∼50% would be longer or shorter than the observed survival time [OST]); imprecise (<33% within 0.67-1.33 times the OST); independently predictive of overall survival (OS); and accurate at deriving scenarios for survival time with approximately 10% of patients dying within a quarter of their EST (worst-case scenario), 50% living within half to double their EST (typical scenario), and 10% living three or more times their EST (best-case scenario). RESULTS: Oncologists' estimates of EST were unbiased (45% were shorter than the OST, 55% were longer); imprecise (29% were within 0.67-1.33 times observed); moderately discriminative (Harrell's C-statistic 0.62, p = .001); and an independently significant predictor of OS (hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; p = .001) in a Cox model including performance status, number of metastatic sites, neutrophil-to-lymphocyte ratio ≥3, treatment group, age, and health-related quality of life (EORTC-QLQC30 physical function score). Scenarios for survival time derived from oncologists' estimates were remarkably accurate: 9% of patients died within a quarter of their EST, 57% lived within half to double their EST, and 12% lived three times their EST or longer. CONCLUSION: Oncologists' estimates of EST were unbiased, imprecise, moderately discriminative, and independently significant predictors of OS. Simple multiples of the EST accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer. IMPLICATIONS FOR PRACTICE: Results of this study demonstrate that oncologists' estimates of expected survival time for their patients with advanced gastric cancer were unbiased, imprecise, moderately discriminative, and independently significant predictors of overall survival. Simple multiples of the expected survival time accurately estimated worst-case, typical, and best-case scenarios for survival time in advanced gastric cancer.

Human papillomavirus in oropharyngeal cancer in Canada: analysis of 5 comprehensive cancer centres using multiple imputation.

BACKGROUND: The incidence of oropharyngeal cancer has risen over the past 2 decades. This rise has been attributed to human papillomavirus (HPV), but information on temporal trends in incidence of HPV-associated cancers across Canada is limited. METHODS: We collected social, clinical and demographic characteristics and p16 protein status (p16-positive or p16-negative, using this immunohistochemistry variable as a surrogate marker of HPV status) for 3643 patients with oropharyngeal cancer diagnosed between 2000 and 2012 at comprehensive cancer centres in British Columbia (6 centres), Edmonton, Calgary, Toronto and Halifax. We used receiver operating characteristic curves and multiple imputation to estimate the p16 status for missing values. We chose a best-imputation probability cut point on the basis of accuracy in samples with known p16 status and through an independent relation between p16 status and overall survival. We used logistic and Cox proportional hazard regression. RESULTS: We found no temporal changes in p16-positive status initially, but there was significant selection bias, with p16 testing significantly more likely to be performed in males, lifetime never-smokers, patients with tonsillar or base-of-tongue tumours and those with nodal involvement (p < 0.05 for each variable). We used the following variables associated with p16-positive status for multiple imputation: male sex, tonsillar or base-of-tongue tumours, smaller tumours, nodal involvement, less smoking and lower alcohol consumption (p < 0.05 for each variable). Using sensitivity analyses, we showed that different imputation probability cut points for p16-positive status each identified a rise from 2000 to 2012, with the best-probability cut point identifying an increase from 47.3% in 2000 to 73.7% in 2012 (p < 0.001). INTERPRETATION: Across multiple centres in Canada, there was a steady rise in the proportion of oropharyngeal cancers attributable to HPV from 2000 to 2012.

Best Practices for Managing Patients with Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer in Canada.

Gastric cancer (GC) is one of the most common types of cancer and is associated with relatively low survival rates. Despite its considerable burden, there is limited guidance for Canadian clinicians on the management of unresectable metastatic GC and gastroesophageal junction cancer (GEJC). Therefore, we aimed to discuss best practices and provide expert recommendations for patient management within the current Canadian unresectable GC and GEJC landscape. A multidisciplinary group of Canadian healthcare practitioners was assembled to develop expert recommendations via a working group. The often-rapid progression of unresectable GC and GEJC and the associated malnutrition have a significant impact on the patient's quality of life and ability to tolerate treatment. Hence, recommendations include early diagnosis, identification of relevant biomarkers to improve personalized treatment, and relevant support to manage comorbidities. A multidisciplinary approach including early access to registered dietitians, personal support networks, and palliative care services, is needed to optimize possible outcomes for patients. Where possible, patients with unresectable GC and GEJC would benefit from access to clinical trials and innovative treatments.

Barriers and Unequal Access to Timely Molecular Testing Results: Addressing the Inequities in Cancer Care Delays across Canada.

Genomic medicine is a powerful tool to improve diagnosis and outcomes for cancer patients by facilitating the delivery of the right drug at the right dose at the right time for the right patient. In 2023, a Canadian conference brought together leaders with expertise in different tumor types. The objective was to identify challenges and opportunities for change in terms of equitable and timely access to biomarker testing and reporting at the education, delivery, laboratory, patient, and health-system levels in Canada. Challenges identified included: limited patient and clinician awareness of genomic medicine options with need for formal education strategies; failure by clinicians to discuss genomic medicine with patients; delays in or no access to hereditary testing; lack of timely reporting of results; intra- and inter-provincial disparities in access; lack of funding for patients to access testing and for laboratories to provide testing; lack of standardized testing; and impact of social determinants of health. Canada must standardize its approach to biomarker testing across the country, with a view to addressing current inequities, and prioritize access to advanced molecular testing to ensure systems are in place to quickly bring innovation and evidence-based treatments to Canadian cancer patients, regardless of their place of residence or socioeconomic status.

Access to Oncology Medicines in Canada: Consensus Forum for Recommendations for Improvement.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients' access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Pathways to adolescent internalizing: early attachment insecurity as a lasting source of vulnerability.

Despite theoretical links between attachment quality in early childhood and subsequent internalizing symptoms, there is limited empirical evidence supporting direct effects. In this article, we test whether early attachment insecurity indirectly contributes to adolescent internalizing by increasing the likelihood of certain pathways leading to elevated symptoms (i.e., moderated mediation). Structural equation modeling and bootstrapping were used to test for moderated mediation using longitudinal data from 910 adolescents participating in the National Institute of Child Health and Human Development Study of Early Child Care (M age = 15.1; 50% female, 23% racial/ethnic minority). Among dyads with a history of an insecure attachment in early childhood, mothers' negative emotions during the transition to adolescence significantly predicted less availability during parent-adolescent interactions, which in turn increased adolescents' preoccupation with parental relationships. The same process was not evident in youth with a history of secure attachments. However, the extent to which preoccupation with parental relationships was associated with increases in internalizing symptoms depended on both attachment history and gender. Results highlight one pathway by which early attachment history may indirectly contribute to increased internalizing symptoms for girls during the transition to adolescence.

Who do we think we are? Analysing the content and form of identity work in the English National Health Service.

PURPOSE: The language used by National Health Service (NHS) "commissioning" managers when discussing their roles and responsibilities can be seen as a manifestation of "identity work", defined as a process of identifying. This paper aims to offer a novel approach to analysing "identity work" by triangulation of multiple analytical methods, combining analysis of the content of text with analysis of its form. DESIGN/METHODOLOGY/APPROACH: Fairclough's discourse analytic methodology is used as a framework. Following Fairclough, the authors use analytical methods associated with Halliday's systemic functional linguistics. FINDINGS: While analysis of the content of interviews provides some information about NHS Commissioners' perceptions of their roles and responsibilities, analysis of the form of discourse that they use provides a more detailed and nuanced view. Overall, the authors found that commissioning managers have a higher level of certainty about what commissioning is not rather than what commissioning is; GP managers have a high level of certainty of their identity as a GP rather than as a manager; and both GP managers and non-GP managers oscillate between multiple identities depending on the different situations they are in. ORIGINALITY/VALUE: This paper offers a novel approach to triangulation, based not on the usual comparison of multiple data sources, but rather based on the application of multiple analytical methods to a single source of data. This paper also shows the latent uncertainty about the nature of commissioning enterprise in the English NHS.

Understanding the work done by NHS commissioning managers: an exploration of the microprocesses underlying day-to-day sensemaking in UK primary care organisations.

PURPOSE: The purpose of this paper is to explore the practical daily work undertaken by middle-level managers in Primary Care Trusts (PCTs), focusing upon the micro-processes by which these managers enact sensemaking in their organisations. DESIGN/METHODOLOGY/APPROACH: The research took a case study approach, undertaking detailed case studies in four PCTs in England. Data collection included shadowing managers, meeting observations and interviews. FINDINGS: The research elucidated two categories of enactment behaviour exhibited by PCT managers: presence/absence; and the production of artefacts. Being "present" in or "absent" from meetings enacted sensemaking over and above any concrete contribution to the meeting made by the actors involved. This paper explores the factors affecting these processes, and describes the situations in which enactment of sense is most likely to occur. Producing artefacts such as meeting minutes or PowerPoint slides also enacted sense in the study sites in addition to the content of the artefact. The factors affecting this are explored. PRACTICAL IMPLICATIONS: The study has practical implications for all managers seeking to maximise their influence in their organisations. It also provides specific evidence relevant to managers working in the new Clinical Commissioning Groups currently being formed in England. ORIGINALITY/VALUE: The study expands the understanding of sensemaking in organisations in two important ways. Firstly, it moves beyond discourse to explore the ways in which behaviours can enact sense. Secondly, it explores the distinction between active and unconscious sensemaking.

Abstracts of the 2023 Canadian Association of Medical Oncologists Annual Scientific Meeting.

On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the abstracts of the 2023 Annual Scientific Meeting. The CAMO Annual Scientific Meeting (ASM) took place on 27 April 2023 in an in-person event in Toronto, ON. Thirty-two (32) abstracts were selected for presentation as oral presentations, in-person poster presentations, and virtual poster presentations. Awards for the top four (4) abstracts were presented during the ASM; they have been marked as "Award Recipient". We congratulate all presenters on their research work and contribution.

Follow-Up Imaging Guidelines for Patients with Stage III Unresectable NSCLC: Recommendations Based on the PACIFIC Trial.

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Use of radiation therapy among patients with Extensive-stage Small-cell lung cancer receiving Immunotherapy: Canadian consensus recommendations.

OBJECTIVES: Thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) are commonly used in the management of extensive-stage small-cell lung cancer (ES-SCLC); however, Phase III trials of first-line immunotherapy often excluded these options. Guidance is needed regarding appropriate use of TRT, PCI, and magnetic resonance imaging (MRI) surveillance while new data are awaited. MATERIALS AND METHODS: In two web-based meetings, a pan-Canadian expert working group of five radiation oncologists and four medical oncologists addressed eight clinical questions regarding use of radiation therapy (RT) and MRI surveillance among patients with ES-SCLC receiving immunotherapy. A targeted literature review was conducted using PubMed and conference proceedings to identify recent (January 2019-April 2022) publications in this setting. Fifteen recommendations were developed; online voting was conducted to gauge agreement with each recommendation. RESULTS: After considering recently available evidence across lung cancer populations and clinical experience, the experts recommended that all patients with a response to chemo-immunotherapy, good performance status (PS), and limited metastases be considered for consolidation TRT (e.g., 30 Gy in 10 fractions). When considered appropriate after multidisciplinary team discussion, TRT can be initiated during maintenance immunotherapy. All patients who respond to concurrent chemo-immunotherapy should undergo restaging with brain MRI to guide decision-making regarding PCI versus MRI surveillance alone. MRI surveillance should be conducted for two years after response to initial therapy. PCI (e.g., 25 Gy in 10 fractions or 20 Gy in 5 fractions) can be considered for patients without central nervous system involvement who have a response to chemo-immunotherapy and good PS. Concurrent treatment with PCI and immunotherapy or with TRT, PCI, and immunotherapy is appropriate after completion of initial therapy. All recommendations were agreed upon unanimously. CONCLUSIONS: These consensus recommendations provide practical guidance regarding appropriate use of RT and immunotherapy in ES-SCLC while awaiting new clinical trial data.

Impact of the COVID-19 Pandemic on Medical Oncology Workload: A Provincial Review.

(1) Background: Cancer is the leading cause of death in Canada, with significant resource limitation impacting the delivery of cancer care nationwide. The onset of the COVID-19 pandemic forced additional resource restriction and diversion, further impacting care delivery. Our intention is to analyze the impact COVID-19 on a provincial medical oncology workload and bring attention to the limitations of the current workload metric for oncologists. (2) Methods: All medical oncology patient encounters were extracted and compared, collected by year and encounter type, from April 2014 through March 2022. (3) Results: There was an increase in all patient encounters by an average of 9.5% per year, including during the strictest COVID-19 restrictions. There was an increase in virtual care encounters from 37.9% to 52.1%. (4) Conclusions: Medical Oncology workloads have increased over time and estimates suggest growing demand. Little data exist to inform workforce requirements and actual workload is not captured by the current metric. Though volume of new consults continues to increase, COVID-19 has highlighted additional changes in the delivery of care, likely with lasting impact, little of which are included in the current workload metric.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Background: Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). Methods: The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. Results: 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5 years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p = 0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Conclusion: Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC.

Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/- chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity.

Lorlatinib Effectiveness and Quality-of-Life in Patients with ALK-Positive NSCLC Who Had Failed Second-Generation ALK Inhibitors: Canadian Real-World Experience.

Lorlatinib is the only targeted therapy approved in Canada to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) whose tumor has progressed despite treatment with second-generation ALK tyrosine kinase inhibitor (TKI), a patient population with high unmet need and lack of publicly reimbursed targeted treatments in Canada. We prospectively examined the real-world effectiveness and impact of lorlatinib on quality-of-life in 59 lorlatinib-treated patients, characterized as: median age of 62.0 years; 47.5% were female; 32.2% had central nervous system metastases; 50.8% had 2+ prior ALK TKI lines; and alectinib was the most common ALK TKI (72.9%) administered before lorlatinib, including 44.1% who received first-line alectinib. With a median follow-up of 15.3 months (IQR: 6.2-19.2), median time-to-treatment discontinuation of lorlatinib was 15.3 months (95% CI: 7.9-not reached), with 54.2% (95% CI: 40.8-65.9%) of patients without treatment discontinuation at 12 months. At baseline, the mean health utility score (HUS) was 0.744 (SD: 0.200). At 3 months, patients receiving lorlatinib demonstrated a 0.069 (95% CI: 0.020-0.118; p = 0.007) average HUS increase over baseline; HUS was maintained at 6 and 12 months. Thus, patients with ALK-positive NSCLC post second-generation ALK TKI remained on lorlatinib for a meaningful duration of time while their quality-of-life was preserved.